The worldwide health problem created by malaria has been made more difficult by the spread of drug-resistant parasites. This project addresses the need for new malaria drugs by initiating preclinical development of one or more candidate(s) from a new class of potent antimalarials. We have developed an orally available and inexpensive class of novel drugs that is expected to act against both chloroquine-resistant and chloroquine-sensitive malaria. We propose to advance a carefully-selected candidate through preclinical steps, leading to a pre-Investigational New Drug meeting with the Food and Drug Administration. With guidance from the FDA, steps that will likely include pharmacokinetics, pharmacodynamics, pharmacology, and toxicity evaluations will be performed in both rats and monkeys. The overall goal will be completion of studies leading to approval of the Investigative New Drug (IND) application for a drug to be used in a Phase-1 human clinical trial.